A variety of medical diseases are beneficially treated by therapeutic agents which are selectively directed to the site of the disease, thereby causing the death of the cells responsible for the disease without harming normal cells. Thus, there is considerable emphasis in the medical technology community focused on obtaining such site directed therapeutic chemicals. Two such diseases where these types of chemicals could be most advantageously applied are atherosclerosis and cancer. We have dealt with atherosclerosis in our above-cited U.S. Pat. No. 4,886,831, but since aspects of the atherosclerosis are applicable to the invention described and claimed herein, these will be discussed below.
Atherosclerosis is a disease associated with occlusion of blood vessels arteries and the like in which fatty substances, particularly lipids, form deposits in the vessels. Such deposits are commonly referred to as "atherosclerotic plaques". Generally, these plaques form as a result of lipids being deposited in and beneath the intima (innermost membrane lining) of arteries and veins. Generally, atherosclerosis involves medium and large-size vessels, with the most commonly affected being the aorta, iliac, femoral, coronary and cerebral arteries. If the disease is not checked, tissues or organs that are distal to the atherosclerotic plaque experience reduced blood flow and thus are adversely affected.
For the most part, atherosclerosis is treated by one of three approaches. First, the vascular regions that are diseased are often replaced by prosthetic or natural grafts. Grafting is a very expensive and medically demanding procedure, and often presents significant associated risks to the patient. The second approach is to put the atherosclerotic patient on drugs, particularly antiarrhythmic, anticoagulant, and plasma lipid lowering chemicals. These substances are also very expensive and the adverse long-term effects of taking them are not known.
A third method has been proposed for treating atherosclerosis. U.S. Pat. No. 4,512,762 describes a photochemical process for destroying atherosclerotic plaques involving the uptake of hematoporphyrin into plaques coupled with lysis of the plaques following irradiation. Unfortunately, this method has two undesirable aspects. First, hematoporphyrin sensitizes patients to subsequent exposure to sunlight. Second, hematoporphyrin is taken up to a significant extent by tissues or cells that surround the plaques. Consequently normal tissue may be destroyed along with the plaques upon subsequent irradiation.
There is a substantial body of literature concerning the treatment of cancer. One regimen, chemical therapy, involves administering drugs to a patient that exert their effects primarily by interrupting DNA synthesis. Such drugs have shown considerable promise and are particularly effective in various combinations when applied to a particular type of cancer. A major drawback associated with chemical therapy, however, is that the therapeutic agent is generally not cell-type specific for cancer cells, but rather is taken up into the DNA of any dividing cell. Consequently, normal cells as well as cancer cells are killed by this treatment. Thus there are severe side effects associated with chemical therapy as it is presently practiced.
One treatment for cancer is described by R. L. Lipson et al., "The Use of a Derivative of Hematoporphyrin in Tumor Detection", J. Natl. Cancer Inst., 26, 1, 1-8, (1961). Hematoporphyrin is injected into a patient experiencing a tumor burden. After injection it is taken up by the tumor. Subsequent irradiation causes lysis of the tumor. Unfortunately, this method has the same drawbacks as treatment of atherosclerosis with hematoporphyrin: the patient may become sensitized to sunlight and there is the likelihood of destruction of normal tissue.